There is evidence both that computer-administered cognitive training can improve ADHD working memory deficits and that this type of training in non-ADHD enhances normal working memory ability by altering brain activity in prefrontal cortex and the parietal lobe. However, no study has characterized brain activity changes following working memory training in ADHD to understand what neural changes occur when cognitive deficits are remedied. This R21 exploratory study will examine the neural basis of cognitive training treatment gains in working memory, ADHD symptoms, and various other executive abilities. The study will compare n=21 ADHD adolescents with evidence for baseline deficits in working memory (i.e., <1.5 SD below normative ratings at baseline) and n=21 demographically-matched non-ADHD healthy control participants. Participants will undergo baseline neuropsychological and fMRI imaging with verbal and visuospatial Sternberg fMRI working memory tasks, 5 weeks of daily computerized working memory training, and then endpoint fMRI and cognitive evaluation of neural and behavioral changes. Training will utilize commercially-available Cogmed software (www.cogmed.com) as it has a well-developed set of computerized tools, with numerous practical advantages for this study. Our analyses will identify which brain regions in ADHD adolescents are affected by working memory treatment and characterize patterns of activation change between baseline and endpoint. We will examine post-treatment differences in the extent of activation and functional connectivity among activated brain regions to test hypotheses about possible neural mechanisms underlying treatment gains. These analyses will provide data that will permit us to confirm a neurobiological model of the treatment mechanism to permit future studies of this intervention's effectiveness in ADHD. We also will conduct a series of analyses to determine what specific changes in brain function might underlie a generalized effect of working memory training on ADHD symptoms and other 'executive'abilities. By identifying the neural correlates any such effect, this study could yield invaluable information about what the neural targets of any effective ADHD treatment must be. The key accomplishment of this exploratory study will be to characterize the neural basis of treatment gains in ADHD by testing theoretically-guided hypotheses about possible neuroplastic changes. The results will support larger, future studies aimed at better understanding the neural basis of this alternative treatment for ADHD, identifying biological or genetic factors that might denote the presence of a remediable working memory deficit, and ultimately achieving a better understanding of the etiology of ADHD working memory deficits. PUBLIC HEALTH RELEVANCE: There is evidence both that computer-administered cognitive training can improve ADHD working memory deficits and that this type of training in non-ADHD enhances normal working memory ability by altering brain activity in prefrontal cortex and the parietal lobe. However, no study has characterized brain activity changes following working memory training in ADHD to understand what neural changes occur when cognitive deficits are remedied. This R21 exploratory study will examine the neural basis of cognitive training treatment gains in working memory, ADHD symptoms, and various other executive abilities.